Is PRDM5 p.Pro403Arg (c.1208C>G) pathogenic?

PRDM5 p.Pro403Arg (c.1208C>G) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9418); No allele count reported in gnomAD v4.1 (AN 1,611,140); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Pro403Arg (c.1208C>G)?

PRDM5 p.Pro403Arg (c.1208C>G) is associated with Cardiovascular phenotype, brittle cornea syndrome 2 (ClinVar).

How common is PRDM5 p.Pro403Arg (c.1208C>G) in the general population?

PRDM5 p.Pro403Arg (c.1208C>G) is no allele count reported in gnomAD v4.1 (AN 1,611,140) (gnomAD).

What do computational predictors say about PRDM5 p.Pro403Arg (c.1208C>G)?

AlphaMissense predicts likely pathogenic (score 0.9418) — an in-silico prediction, not a clinical call.

PRDM5 p.Pro403Arg

c.1208C>G · rs769647986 · VCV1339868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9418 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,140)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9418	likely pathogenic
REVEL	0.46	indeterminate
SaProt	LLR -10.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,140). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRDM5
Protein: p.Pro403Arg
Coding: c.1208C>G
MANE Select: NM_018699
dbSNP: rs769647986
Type: single nucleotide variant
Location: chr4:120785072 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB

Full PRDM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brittle cornea syndrome 2

Similar variants

PRDM5 p.Pro403Leu Uncertain significance ★★ ⚠ same residue
PRDM5 p.Pro403= Likely benign ★★ same residue
PRDM5 c.1623+1G>A Likely pathogenic ★★ same condition
PRDM5 c.865+1G>A Likely pathogenic ★★ same condition
PRDM5 p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 p.Arg346Ter Pathogenic ★★ same condition
PRDM5 p.Gln420Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 p.Gln556Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prdm5-p-pro403arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown